Leung, Lester Y.

Background: White matter disease (WMD) and silent brain infarction (SBI) are known to be risk markers for dementia. Nevertheless, the effects of incidentally-discovered WMD and SBI on routinely-obtained neuroimages is unknown. Methods: In the retrospective cohort study, Kaiser Permanente-Southern California (KPSC) health plan enrollees aged ≥ 50 years old with a brain cross-sectional image (CT or MRI) between 2009-2019 and without a prior history of ischemic stroke, transient ischemic attack, or dementia were identified. Natural language processing (NLP) was used to identify patients with SBI and WMD on the first qualifying neuroimaging report. Cox proportional hazards regression model was applied to estimate the effects of WMD and SBI on dementia, controlling for major cardiovascular risk factors. Results: Among 262,875 individuals receiving brain neuroimaging, 13,154 (5.0%) and 78,330 (29.8%) had SBI and WMD, respectively. The table below summarizes the crude dementia incidence rates. The crude hazard ratio (HR) was 3.69 (95% CI 3.58-3.80) for WMD and 2.80 (95% CI 2.68-2.93) for SBI. In the multivariable model controlling for all major cardiovascular risk factors, the effect of WMD on dementia risk was found to be stronger in younger compared to older patients and for CT- compared to MRI-discovered lesions. With CT, the adjusted HR was 3.08 (95% CI 2.84-3.34) for those < age 70 and 1.90 (95% CI 1.83-1.97) for those ≥ age 70. With MRI, the adjusted HR was 2.58 (95% CI 2.31-2.87) for those < age 70 and 1.59 (95% CI 1.45-1.75) for those ≥ age 70. The adjusted HR associated with a finding of SBI was 2.01 (95% CI 1.78-2.32) for patients age <70 and 1.26 (95% CI 1.20-1.32) for patients age ≥70, and was not modified by imaging modality. Conclusion: Incidentally-discovered WMD and SBI are common in patients ≥ age 50 and are associated with substantial increase in the risk of subsequent dementia. The findings may represent an opportunity for dementia prevention.

Introduction: Silent brain infarcts (SBIs) and white matter disease (WMD) are highly prevalent and associated with increased risk of ischemic stroke in patients with traditional stroke risk factors (RFs) in prospective cohort studies. Their frequency and associations with stroke RFs have not been well described in real world populations. Methods: This was a cross-sectional study of patients age ≥ 50 in the Kaiser Permanente-Southern California (KPSC) health system between 2009-2019 with a head CT or MRI for non-stroke indications and no history of ischemic stroke, transient ischemic attack, or dementia. A natural language processing (NLP) algorithm developed at Mayo Clinic and Tufts Medical Center was applied to the KPSC EHR to identify individuals with reported SBIs or WMD. Multivariable Poisson regression with robust error variance was used to estimate risk ratios of demographics, stroke RFs (from the Framingham Stroke Risk Score), and scan modality on the presence of SBIs or WMD. Results: Among 262,875 individuals, the NLP identified 13,154 (5.0%) with SBIs and 78,330 (29.8%) with WMD. Stroke RFs were highly prevalent in this cohort. The majority underwent CTs (74.8%) instead of MRIs as their initial neuroimaging. After adjustment for demographics and RFs, advanced age demonstrated a strong association with increased risk of SBIs and WMD (table). MRI was associated with a reduced risk of reported SBIs (ARR: 0.87, 95% CI 0.83-0.91) and an increased risk of reported WMD (ARR 2.86, 95% CI 2.83-2.90). Despite being prevalent, traditional stroke RFs had weak associations with increased risk of SBIs or increased risk of WMD. Conclusions: Advanced age is strongly associated with incidentally discovered SBIs and WMD on neuroimaging studies obtained in routine care. The development of SBIs and WMD may not be fully attributable to traditional stroke RFs.